Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1172728 | ENA |
REPOSITORIES: ENA
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Project description:It was previously reported that inhibition of autophagosome formation by MRT68921 induced accumulation of cytosolic dsDNA, which can activate cytosolic DNA-sensor signaling pathway, thereby reducing cell viability through reactive oxygen species generation in leukemia cells. Thus, we examined the effect of combination treatment of MRT68921 and a leukemia differentiation therapeutic drug, all-trans retinoic acid.
2024-03-05 | GSE193056 | GEO
Project description:The ability of dying cells to activate antigen presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here we show that engulfed cells only containing cytosolic dsDNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs, via extrinsic STING-signaling. HEK293 cells containing double strand DNA robustly induced the production of cytokines in macrophages that was dependent on extrinsic STING signaling within the macrophage.
2018-09-04 | GSE110929 | GEO
Project description:Analysis of dsDNA-induced innate immune response at gene expression level. The hypothesis tested in this study was that K224R mutation significantly inhibits hSTING activity. Results provide important information of the response of hSTING and its variants to cytosolic dsDNA, such as induction of type I IFN genes and proinflammatory cytokine genes.
2017-02-14 | GSE94845 | GEO
Project description:Bacterial species from diverse phyla contain multiple replicons, yet how these multipartite genomes are organized and segregated during the cell cycle remains poorly understood. Agrobacterium tumefaciens has a 2.8 Mb circular chromosome (Ch1), a 2.1 Mb linear chromosome (Ch2), and two large plasmids (pAt and pTi). We used this alpha proteobacterium as a model to investigate the global organization and temporal segregation of a multipartite genome. Using Chromosome Conformation Capture (Hi-C) assays, we demonstrate that both the circular and the linear chromosomes but neither of the plasmids have their left and right arms juxtaposed from their origins to their termini, generating inter-arm interactions that require the broadly conserved structural maintenance of chromosomes (SMC) complex. Moreover, our studies revealed two types of inter-replicon interactions: “ori-ori clustering” in which the replication origins of all four replicons interact, and “Ch1-Ch2 alignment” in which the arms of Ch1 and Ch2 interact linearly along their lengths. We show that the centromeric proteins (ParB1 for Ch1 and RepBCh2 for Ch2) are required for both types of inter-replicon contacts. Finally, using fluorescence microscopy, we validated the clustering of the origins and observed their frequent colocalization during segregation. Altogether, our findings provide a high-resolution view of the conformation of a multipartite genome. We hypothesize that inter-centromeric contacts promote the organization and maintenance of diverse replicons.
2022-01-30 | GSE182881 | GEO
Project description:Antimicrobial resistance (AMR) arises from complex genetic and regulatory changes, including single mutations, gene acquisitions or cumulative effects. Advancements in genomics and proteomics facilitate more comprehensive understanding of the mechanisms behind antimicrobial resistance. In this study, 74 clinically obtained Klebsiella pneumoniae isolates with increased meropenem and/or imipenem MICs were characterized by broth microdilution and PCR to check for the presence of carbapenemase genes. Subsequently, a representative subset of 15 isolates was selected for whole genome sequencing (WGS) by Illumina and Nanopore sequencing, and proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the mechanisms underlying the differences in carbapenem susceptibility of Klebsiella pneumoniae isolates. Identical techniques were applied to characterize 4 mutants obtained after sequential meropenem exposure. We demonstrated that in clinically obtained isolates, increased copy numbers of blaOXA-48 containing plasmids, combined with OmpK36 loss, contributed to high carbapenem MICs without involvement of OmpK35 or other porins or efflux systems. In the meropenem exposed mutants, increased copy numbers of blaCTX-M-15 or blaOXA-48 containing plasmids, combined with OmpK36 loss was demonstrated. The OmpK36 loss resulted from the insertion of IS1 transposable elements or partial deletion of the ompK36 gene. Additionally, we identified two mutations, C59A and C58A, in the DNA coding the copA antisense RNA of IncFII plasmids and multiple mutations of an IncR plasmid, associated with increased plasmid copy numbers. This study demonstrates that by combining WGS and LC-MS/MS, the effect of genomic changes on protein expression related to antibiotic resistance and the mechanisms behind antibiotic resistance can be elucidated.
2025-06-06 | PXD061983 | Pride
Project description:AIM: By adopting comparative transcriptomic approach, we investigated the gene expression of wood decomposing Basidiomycota fungus Phlebia radiata. Our aim was to reveal how hypoxia and lignocellulose structure affect primary metabolism and the expression of wood decomposition related genes. RESULTS: Hypoxia was a major regulator for intracellular metabolism and extracellular enzymatic degradation of wood polysaccharides by the fungus. Our results manifest how oxygen depletion affects not only over 200 genes of fungal primary metabolism but also plays central role in regulation of secreted CAZyme (carbohydrate-active enzyme) encoding genes. Based on these findings, we present a hypoxia-response mechanism in wood-decaying fungi divergent from the regulation described for Ascomycota fermenting yeasts and animal-pathogenic species of Basidiomycota.
2020-02-01 | GSE141153 | GEO
Project description:Carcinoma-astrocyte gap junctions promote brain metastasis by cytosolic dsDNA response transfer
| PRJNA315285 | ENA
Project description:Borrelia burgdorferi, the tick-transmitted spirochete agent of Lyme disease, has a highly segmented genome with a linear chromosome and various linear or circular plasmids. Here, by imaging several chromosomal loci and 16 distinct plasmids, we show that B. burgdorferi is polyploid during growth in culture and that the number of genome copies decreases during stationary phase. B. burgdorferi is also polyploid inside fed ticks and chromosome copies are regularly spaced along the spirochete’s length in both growing cultures and ticks. This patterning involves the conserved DNA partitioning protein ParA whose localization is controlled by a potentially phage-derived protein, ParZ, instead of its usual partner ParB. ParZ binds its owe coding region and acts as a centromere-binding protein. While ParA works with ParZ, ParB controls the localization of the condensin, SMC. Together, the ParA/ParZ and ParB/SMC pairs ensure faithful chromosome inheritance. Our findings underscore the plasticity of cellular functions, even those as fundamental as chromosome segregation.
2022-10-28 | GSE202255 | GEO
Project description:<p>The study of antimicrobial resistance (AMR) in infectious diarrhea has generally been limited to cultivation, antimicrobial susceptibility testing and targeted PCR assays. When individual strains of significance are identified, whole genome shotgun (WGS) sequencing of important clones and clades is performed. Genes that encode resistance to antibiotics have been detected in environmental, insect, human and animal metagenomes and are known as "resistomes". While metagenomic datasets have been mined to characterize the healthy human gut resistome in the Human Microbiome Project and MetaHIT and in a Yanomani Amerindian cohort, directed metagenomic sequencing has not been used to examine the epidemiology of AMR. Especially in developing countries where sanitation is poor, diarrhea and enteric pathogens likely serve to disseminate antibiotic resistance elements of clinical significance. Unregulated use of antibiotics further exacerbates the problem by selection for acquisition of resistance. This is exemplified by recent reports of multiple antibiotic resistance in Shigella strains in India, in Escherichia coli in India and Pakistan, and in nontyphoidal Salmonella (NTS) in South-East Asia. We propose to use deep metagenomic sequencing and genome level assembly to study the epidemiology of AMR in stools of children suffering from diarrhea. Here the epidemiology component will be surveillance and analysis of the microbial composition (to the bacterial species/strain level where possible) and its constituent antimicrobial resistance genetic elements (such as plasmids, integrons, transposons and other mobile genetic elements, or MGEs) in samples from a cohort where diarrhea is prevalent and antibiotic exposure is endemic. The goal will be to assess whether consortia of specific mobile antimicrobial resistance elements associate with species/strains and whether their presence is enhanced or amplified in diarrheal microbiomes and in the presence of antibiotic exposure. This work could potentially identify clonal complexes of organisms and MGEs with enhanced resistance and the potential to transfer this resistance to other enteric pathogens.</p> <p>We have performed WGS, metagenomic assembly and gene/protein mapping to examine and characterize the types of AMR genes and transfer elements (transposons, integrons, bacteriophage, plasmids) and their distribution in bacterial species and strains assembled from DNA isolated from diarrheal and non-diarrheal stools. The samples were acquired from a cohort of pediatric patients and controls from Colombia, South America where antibiotic use is prevalent. As a control, the distribution and abundance of AMR genes can be compared to published studies where resistome gene lists from healthy cohort sequences were compiled. Our approach is more epidemiologic in nature, as we plan to identify and catalogue antimicrobial elements on MGEs capable of spread through a local population and further we will, where possible, link mobile antimicrobial resistance elements with specific strains within the population.</p>
| phs001260 | dbGaP